RESUMO
During the screening of fungi for inhibitors of squalene synthase, Phoma sp. C2932 was found to produce three structurally related novel inhibitors. These compounds, designated the squalestatins, exhibited potent activity against both mammalian (rat liver) and fungal (Candida albicans) squalene synthase. Furthermore, they also had broad spectrum in vitro antifungal activity.
Assuntos
Antifúngicos/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes , Compostos Bicíclicos com Pontes/farmacologia , Farnesil-Difosfato Farnesiltransferase/antagonistas & inibidores , Ácidos Tricarboxílicos/farmacologia , Animais , Antifúngicos/química , Antifúngicos/isolamento & purificação , Compostos Bicíclicos com Pontes/química , Compostos Bicíclicos com Pontes/isolamento & purificação , Fungos/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Ratos , Ácidos Tricarboxílicos/química , Ácidos Tricarboxílicos/isolamento & purificaçãoRESUMO
A novel antifungal antibiotic GR135402 has been isolated from a fermentation broth of Graphium putredinis which inhibited protein synthesis in Candida albicans but not rabbit reticulocytes. The spectrum of activity included C. albicans and Cryptococcus neoformans but not some other Candida species or Aspergillus species. Therapeutic efficacy in a mouse model of systemic candidosis was attained following parenteral dosing.
Assuntos
Antifúngicos/química , Antifúngicos/isolamento & purificação , Fungos Mitospóricos/química , Compostos Policíclicos/química , Compostos Policíclicos/isolamento & purificação , Inibidores da Síntese de Proteínas/química , Inibidores da Síntese de Proteínas/isolamento & purificação , Animais , Antifúngicos/farmacologia , Aspergillus/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Fermentação , Camundongos , Testes de Sensibilidade Microbiana , Fungos Mitospóricos/classificação , Compostos Policíclicos/farmacologia , Inibidores da Síntese de Proteínas/farmacologiaRESUMO
The uptake of some ionogenic radiopharmaceuticals may be explained on the basis of a pH shift theory. An HPLC method for pKa measurement has been developed for radiotracers. It has been tested with several amines and used to estimate the pKsa (pKa in the mixed solvent 30% acetonitrile-water) of some 99mTc-PnAO complexes by observing the change in capacity factor k' with change in mobile phase pH. The non-ionogenic complexes Tc-PnAO and Tc-DE-PnAO showed constant k' values while the ionogenic complexes Tc-MNE-PnAO and Tc-IP-PnAO had pKsa values of about 6.6 and 8.3. The method is reproducible and is applicable to nearly all ionogenic radiopharmaceuticals.